Bad neighbours: hypoxia and genomic instability in prostate cancer
| العنوان: | Bad neighbours: hypoxia and genomic instability in prostate cancer |
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| المؤلفون: | Robert G. Bristow, Jack Ashton |
| المصدر: | The British Journal of Radiology Ashton, J & Bristow, R 2020, ' Bad neighbours : hypoxia and genomic instability in prostate cancer ', The British journal of radiology, pp. 20200087 . https://doi.org/10.1259/bjr.20200087 |
| بيانات النشر: | British Institute of Radiology, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, Genome instability, DNA Repair, DNA repair, Disease, Somatic evolution in cancer, Genomic Instability, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, medicine, Humans, PTEN, Radiology, Nuclear Medicine and imaging, Homologous Recombination, Nucleic Acid Synthesis Inhibitors, 030304 developmental biology, 0303 health sciences, biology, business.industry, Prostatic Neoplasms, General Medicine, Hypoxia (medical), medicine.disease, Advances in radiation biology – Highlights from 16th ICRR special feature: Review Article, 030220 oncology & carcinogenesis, Disease Progression, Cancer research, biology.protein, Tumor Hypoxia, medicine.symptom, Homologous recombination, business |
| الوصف: | Prostate cancer (PCa) is a clinically heterogeneous disease and has poor patient outcome when tumours progress to castration-resistant and metastatic states. Understanding the mechanistic basis for transition to late stage aggressive disease is vital for both assigning patient risk status in the localised setting and also identifying novel treatment strategies to prevent progression. Subregions of intratumoral hypoxia are found in all solid tumours and are associated with many biologic drivers of tumour progression. Crucially, more recent findings show the co-presence of hypoxia and genomic instability can confer a uniquely adverse prognosis in localised PCa patients. In-depth informatic and functional studies suggests a role for hypoxia in co-operating with oncogenic drivers (e.g. loss of PTEN) and suppressing DNA repair capacity to alter clonal evolution due to an aggressive mutator phenotype. More specifically, hypoxic suppression of homologous recombination represents a “contextual lethal“ vulnerability in hypoxic prostate tumours which could extend the application of existing DNA repair targeting agents such as poly-ADP ribose polymerase inhibitors. Further investigation is now required to assess this relationship on the background of existing genomic alterations relevant to PCa, and also characterise the role of hypoxia in driving early metastatic spread. On this basis, PCa patients with hypoxic tumours can be better stratified into risk categories and treated with appropriate therapies to prevent progression. |
| تدمد: | 1748-880X 0007-1285 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::41641e767c87c7ba6547e6b144c0cbac https://doi.org/10.1259/bjr.20200087 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....41641e767c87c7ba6547e6b144c0cbac |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1748880X 00071285 |
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